Genetic polymorphism of the angiotensin-converting enzyme (ACE) in asthmatic patients.

Angiotensin-converting enzyme (ACE) inactivates bradykinin, substance P and neurokinin A, which are believed to play important roles in the pathogenesis of asthma, especially in neurogenic inflammation. It has recently been shown that an insertion (I)/deletion (D) polymorphism in the ACE gene accounts for variation in serum ACE levels. There are thus three genotypes (insertion homozygote, II; deletion homozygote, DD; heterozygotes, DI). The serum ACE level with the DD type is reported to be about double that of the II type and intermediate in the DI case. In the present study, we examined whether asthma is linked with this ACE gene polymorphism. Seventy-one patients with asthma (27 males and 44 females) and 142 sex- and age-matched healthy controls were determined for their genotype by the polymerase chain reaction (PCR) method. Twenty-five asthmatics demonstrated the II type (35.2%), 37 the DI type (52.1%), and nine the DD type (12.7%). There were no significant differences in the distributions of genotypes and serum ACE levels between healthy controls and patients. No significant differences were evident in serum IgE levels, age at onset, proportion of atopic type patients and severity of asthma among the three genotypes. We did not find any association between asthma and the ACE gene polymorphism in this study.

Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis.

OBJECTIVE: Soluble HLA class I antigens (sHLAs) in human serum have been reported to be associated with allografts and autoimmune disease and could modify immunological reactions induced by membrane type HLAs. To investigate the clinical significance of sHLAs in sarcoidosis, we assessed concentrations of sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined their production by peripheral blood mononuclear cells (PBMCs) and BALF cells. METHODS: Concentrations of sHLAs were determined by enzyme-linked immunosorbent assay, using a monoclonal antibody against HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta2-microglobulin. PBMCs and BALF cells were cultured in the presence or absence of either LPS or PHA. PATIENTS: Serum levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy control subjects. sHLAs concentrations in BALF were also investigated in 17 active sarcoidosis patients and in 13 control subjects. RESULTS: sHLAs levels in both serum and BALF were higher in sarcoidosis cases than in control subjects (p<0.05, in both). In the patients, values were significantly higher in active than in inactive stages (p<0.001) and significantly correlated with angiotensin-converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced amounts of sHLAs in patients with active sarcoidosis compared with those in control subjects. CONCLUSION: These results demonstrated that the level of sHLAs in serum is a useful index of disease activity of sarcoidosis, partly reflecting production by PBMCs and BALF cells.

[Clinical efficacy of ceftriaxone when administered once daily for respiratory tract infections in patients with advanced ages].

Ceftriaxone (CTRX), a new third generation cephalosporin, was investigated upon once daily administration for its clinical efficacy and safety on respiratory tract infections in patients with advanced ages. The results are summarized as follows: 1. Clinical responses to CTRX of 48 cases of advanced age patients with respiratory tract infections were good with an efficacy rate of 89.6%. 2. Adverse reactions to CTRX were mainly exanthema in 7 cases (14.6%). 3. Serum levels of CTRX were determined in 4 cases after intravenous drip infusion of 2 g CTRX. Serum levels were analyzed by one-compartment model. There was no evidence of accumulation of CTRX in the patients with advanced ages.

[Serum levels of solubule tumor necrosis factor (TNF) receptors in patients with pulmonary tuberculosis].

Tumor necrosis factor alpha (TNF-alpha) is released from cells of monocyte/macrophage lincage and mediates the development of a variety of clinical and pathomorphological features in various infectious diseases, autoimmune diseases and cancer. In the case of tuberculosis, it is suggested that the release of TNF-alpha in the affected regions and into the circulation could account for the pathological and clinical features such as the development of necrotic lesions and fever and weight loss in TB patients. In the present study, the levels of soluble TNF receptor type I (sTNFR type I) and type II (sTNFR type II) and TNF-alpha in the sera of patients with pulmonary TB were assayed, and we tried to know whether these levels have clinical significance in determining the disease activity in TB patients. The serum levels of both sTNFR types I and II were significantly higher in TB patients (n = 22) who were previously untreated than in the healthy control (n = 14): for sTNFR type I, 2.82 +/- 1.37 ng/ml vs. 1.40 +/- 0.33 ng/ml (p < 0.0001), and for sTNFR type II, 3.83 +/- 1.76 ng/ml vs. 1.62 +/- ng/ml (p < 0.0001). The serum levels of sTNFR types I and II in TB patients showed significant correlations with their serum levels of CRP. The serum levels of TNF-alpha in these TB patients was 2.21 +/- 1.72 pg/ml, whereas TNF-alpha was not detectable in the sera of 9 healthy control. The serum levels of sTNFR type I and II were significantly higher in cavitary TB (n = 17) than in non-cavitary TB (n = 5). When TB patients were treated with antituberculosis drugs and clinical improvements were achieved, the elevated levels of sTNFR type I and TNF-alpha in the sera of same 5 patients measured before starting treatment showed significant decline and the serum levels of sTNFR type II showed also declined, however, the decline was statistically not significant. From all the results obtained in this study, we conclude that the assay of the serum levels of sTNFR in TB patients is useful in the evaluation of the disease activity of TB.